Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source

Murrie, Rhiannon P.; Werdiger, Freda; Donnelley, Martin; Lin, Yu-Chieh; Carnibella, Richard; Samarage, Chaminda R.; Pinar, Isaac; Preissner, Melissa; Wang, Jiping; Li, Jian; Morgan, Kaye S.; Parsons, David; Dubsky, Stephen; Fouras, Andreas

doi:10.1038/s41598-019-57376-w

Cited by 26 publications

(23 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Semi-automated segmentation of CT images is commonly used to define total lung volume in healthy and diseased mice 15 , 19 , 33 – 37 , hence we used this method in this study as a benchmark for correlation of lung volumes. However, poor resolution owing to low signal-to-noise-ratio and motion induced image blurring could limit the lung volume quantification using retrospectively gated CT 38 .…”

Section: Discussionmentioning

confidence: 99%

Simple low dose radiography allows precise lung volume assessment in mice

Khan

Markus

Rittmann

et al. 2021

Sci Rep

View full text Add to dashboard Cite

X-ray based lung function (XLF) as a planar method uses dramatically less X-ray dose than computed tomography (CT) but so far lacked the ability to relate its parameters to pulmonary air volume. The purpose of this study was to calibrate the functional constituents of XLF that are biomedically decipherable and directly comparable to that of micro-CT and whole-body plethysmography (WBP). Here, we developed a unique set-up for simultaneous assessment of lung function and volume using XLF, micro-CT and WBP on healthy mice. Our results reveal a strong correlation of lung volumes obtained from radiographic XLF and micro-CT and demonstrate that XLF is superior to WBP in sensitivity and precision to assess lung volumes. Importantly, XLF measurement uses only a fraction of the radiation dose and acquisition time required for CT. Therefore, the redefined XLF approach is a promising tool for preclinical longitudinal studies with a substantial potential of clinical translation.

show abstract

Section: Discussionmentioning

confidence: 99%

Simple low dose radiography allows precise lung volume assessment in mice

Khan

Markus

Rittmann

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This study successfully shows that XV-when performed on a laboratory source 25 -can capture and differentiate a range of lung disease presentations seen in β-ENaC mice via the novel quantification methods described here. Currently, clinically feasible methods for the quantification of regional lung airflows and heterogeneity are sparse, but this study shows that it is possible to measure the dynamics of muco-obstructive disease presentations in large groups of animals using XV without the need for a synchrotron X-ray source.…”

Section: Discussionmentioning

confidence: 77%

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry

Werdiger

Donnelley

Dubsky

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases. Cystic fibrosis (CF) is a progressive, chronic and debilitating genetic disease caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. Unrelenting CF airway disease begins early in infancy and produces a steady deterioration in quality of life, ultimately leading to premature death. Effective lung health assessment tools must capture the patchy nature of muco-obstructive lung diseases such as cystic fibrosis, and this is particularly important during the early stages of the disease when local treatments could be applied to prevent disease progression. Assessments of overall lung health in humans and animals are typically made using lung function tests that screen for abnormalities by measuring the flow of gas in the airways. Spirometry is the most common tool for assessing lung function, however it measures global airflow at the mouth. This means that parameters such as FEV 1 are a single, global measure of the health of the entire lung, are effort-dependent, and provide no information about the location of muco-obstructive disease. Multiple breath wash-in or wash-out techniques that measure the lung-clearance index (LCI) are sensitive to some changes in CF disease as they reflect the health of both the small and large airways 1, 2 , but can only provide limited regional airflow information. LCI is rarely reported in laboratory animal studies. The forced oscillation technique (FOT) measures the resistive properties of the respiratory system and has been used in obstructive lung disease assessment, although the re...

show abstract

“…These parameters can vary tremendously depending on the employed X-ray source and intention of the experiment. At synchrotrons and liquid-metal jet sources, single-frame acquisition times around 20 ms have been demonstrated for mechanically ventilated small-animal models (Stahr et al, 2016;Murrie et al, 2020). In these two set-ups, respiratory cycles lasted 0.45 s and 0.5 s during the acquisition of the CT. Consequently, data were taken at multiple positions in the respiratory cycle within the duration of a single CT scan, while only one frame per respiratory cycle was recorded in the proof-of-principle experiment at the MuCLS.…”

Section: Propagation-based Phase-contrast Imagingmentioning

confidence: 99%

“…For a sharp CT result, all projection images of a single CT have to be recorded at the same position in the respiratory cycle. Considering this boundary condition, a full tomography can be acquired about a factor of two faster with the reported parameters (Stahr et al, 2016;Murrie et al, 2020) compared with the MuCLS. However, pushing the total acquisition time to the smallest possible value was not the objective of the proof-of-principle experiment presented above.…”

Section: Propagation-based Phase-contrast Imagingmentioning

confidence: 99%

The versatile X-ray beamline of the Munich Compact Light Source: design, instrumentation and applications

et al. 2020

View full text Add to dashboard Cite

Inverse Compton scattering provides means to generate low-divergence partially coherent quasi-monochromatic, i.e. synchrotron-like, X-ray radiation on a laboratory scale. This enables the transfer of synchrotron techniques into university or industrial environments. Here, the Munich Compact Light Source is presented, which is such a compact synchrotron radiation facility based on an inverse Compton X-ray source (ICS). The recent improvements of the ICS are reported first and then the various experimental techniques which are most suited to the ICS installed at the Technical University of Munich are reviewed. For the latter, a multipurpose X-ray application beamline with two end-stations was designed. The beamline's design and geometry are presented in detail including the different set-ups as well as the available detector options. Application examples of the classes of experiments that can be performed are summarized afterwards. Among them are dynamic in vivo respiratory imaging, propagation-based phase-contrast imaging, grating-based phase-contrast imaging, X-ray microtomography, K-edge subtraction imaging and X-ray spectroscopy. Finally, plans to upgrade the beamline in order to enhance its capabilities are discussed.

show abstract

Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source

Cited by 26 publications

References 27 publications

Simple low dose radiography allows precise lung volume assessment in mice

Simple low dose radiography allows precise lung volume assessment in mice

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry

The versatile X-ray beamline of the Munich Compact Light Source: design, instrumentation and applications

Contact Info

Product

Resources

About